Umpolung Reactivity of Indole through Gold Catalysis

Electrophilic indole? Indoles, which are typically nucleophilic, can be made electrophilic through gold catalysis. By using an ortho-azido group to deliver a nitrene intramolecularly, an arylalkyne is converted into a gold carbene intermediate containing an indole skeleton that is highly electrophilic at the 3-position. A range of functionalized indoles is readily accessed by utilizing this strategy.     

Umpolung Reactivity of Aldehydes toward Carbon Dioxide

Carbon dioxide is an intrinsically stable molecule. Therefore, its activation requires extra energy input in the form of reactive reagents and/or activated catalysts and, often, harsh reaction conditions. Reported here is a direct carboxylation reaction of aromatic aldehydes with carbon dioxide to afford α‐keto acids as added‐value products. In situ generation of a reactive cyanohydrin was the key to the successful carboxylation reaction under operationally mild reaction conditions (25–40 °C, 1 atm CO₂). The resulting α‐keto acids served as a platform for α‐amino acid synthesis by reductive amination reactions, illustrating the chemical synthesis of essential bioactive molecules from carbon dioxide.     

Reactivity Umpolung of Tertiary Amide Enabled by Catalytic Reductive Stannylation

Reactivity umpolung is an important concept in organic chemistry. Established reactivity umpolung mainly focuses on the aldehyde and umpolung of amide carbonyl group is not known. In this report, we describe a process to obtain the umpolung reactivity of tertiary amide. This process hinges on the efficient reductive stannylation catalyzed by Ir/silane and facile Sn−Li exchange. By leveraging this umpolung reactivity, drug Fluoxetine was derivatized to 12 different analogues via reacting with various electrophiles and four biologically active molecules were prepared concisely. This unlocked umpolung reactivity of tertiary amide is expected to find applications to synthesize complex amines from amides.     

An Apparent Umpolung Reactivity of Indole through [Au]-Catalysed Cyclisation and Lewis-Acid-Mediated Allylation

The sequential functionalization of indole C2 and C3 in an umpolung fashion was executed with a predesigned substrate and choice of reagents. The developed method comprises gold-catalysed alkynol cycloisomerisation/intramolecular addition of C2 of indole and subsequent BF₃ ⋅ OEt₂-mediated regioselective C3 allylation, resulting in the synthesis of the functionalized indoloisoquinolinone scaffold. The reaction involves 5-endo-alkynol cycloisomerisation and the dearomative addition of indole C2 to the intermediate oxocarbenium cation, which results in two equilibrating fused and spiropentacyclic intermediates, which upon treatment with allyl silane in the presence of BF₃ ⋅ OEt₂, undergo selective indole C3 allylation. Other nucleophiles, such as hydride, azide and indole, were also found to be compatible with this process.     

经过极性反转的亲核有机催化

总结了近几年来经过极性反转的有机催化的研究近展, 概括了以C, N, P, S为中心的各种亲核催化剂的催化机理及催化性能. 通过对不同类别及同类不同活性中心的催化剂的比较分析, 简要概括了各种催化剂的优劣势, 并对极性反转的有机过程进行了机理上的阐述.     

Keteniminium-Driven Umpolung Difunctionalization of Ynamides

A three-component Pd-catalyzed coupling of ynamides, aryl diazonium salts, and aryl boronic acids for the synthesis of novel triaryl-substituted enamides is described. This transformation represents the first example of an umpolung regioselective unsymmetrical syn-1,2-diarylation/aryl-olefination of ynamides. The aryl moieties of the diazonium salt (electrophile) and boronic acid (nucleophile) are explicitly incorporated in the electrophilic α- and nucleophilic β-position, respectively, of the ynamide, resulting in a single isomer of the N-bearing tetrasubstituted olefin. The scope is broad (68 examples), showing excellent functional-group tolerance. DFT calculations substantiate the rationale of the mechanistic cycle and the regioselectivity. The chemoselectivity and synthetic potential of the enamide products were also studied.     

Synthesis and Stereoselective Reactions of New Stable α-Ferrocenyllithium Derivatives. An Umpolung of the Ferrocene Reactivity

The reductive lithiation of various α-ferrocenylcarbinol derivatives yields stable α-ferrocenyllithium species (see scheme). These can be quenched with different electrophiles with complete retention of configuration.     

经典有机反应中的极性反转

极性反转是有机化学中的一个基本概念,是有机合成中C―C键形成的有效方法。本文结合近期文献总结了极性反转的基本类型,并讨论了相关机理,以供基础有机化学教学之参考。     

Umpolung of Amine Reactivity. Nucleophilic α-(Secondary Amino)-alkylation via Metalated Nitrosamines

There are basically two kinds of hetero atoms in organic molecules: one kind confers electrophilic character upon the carbon atom to which it is bound, and the other kind turns it into a nucleophilic site. The development of methods permitting transitions between the two resulting categories of reagents has become an important task of modern organic synthesis. The scope of such umpolung of the reactivity of functional groups is discussed for the case of amines as an example. A method of preparing masked α-secondary amino carbanions consists in nitrosation of the secondary amine, followed by metalation of the resulting nitrosamine α-to the nitrogen, reaction with electrophiles, and subsequent denitrosation. Many examples are given for each of these steps which illustrate the wide scope of the overall synthetic operation (electrophilic substitution at the α-C atom of the secondary amine). Preliminary applications and a method for avoiding the handling of nitrosamines are presented, and the report concludes with a brief account of the significance of nitrosamines in the study of carcinogenesis and mutagenesis.     

Umpolung Reactivity of Ynamides: An Unconventional [1,3]‐Sulfonyl and [1,5]‐Sulfinyl Migration Cascade

A regioselective sulfonyl/sulfinyl migration cycloisomerization cascade of alkyne‐tethered ynamides is developed in the presence of XPhosgold catalyst. This reaction is the first example of a general [1,3]‐sulfonyl migration from the nitrogen center to the β‐carbon atom of ynamides, followed by umpolung 5‐endo‐dig cyclization of the ynamide α‐carbon atom to the gold‐activated alkyne, and final deaurative [1,5]‐sulfinylation. This process allows the synthesis of peripherally decorated unconventional 4‐sulfinylated pyrroles with broad scope from N‐propargyl‐tethered ynamides. In contrast, N‐homopropargyl‐tethered ynamides undergo intramolecular tetradehydro Diels–Alder reaction to provide 2,3‐dihydro‐benzo[f]indole derivatives. Control experiments and density‐functional theory studies were used to study the reaction pathways.     

有机反应中的极性转化方法

极性转换方法是一种重要的有机合成新方法 ,对极性转换的概念和应用作了论述 ,并对一些极性转换的新技术作了简介     

Polarity Umpolung Strategy for the Radical Alkylation of Alkenes

Free radical mediated alkylation of alkenes is a challenging and largely unmet goal. Disclosed here is a conceptually novel “polarity umpolung” strategy for radical alkylation of alkenes using a portfolio of easily accessed, difunctional alkylating reagents. This strategy is achieved by substituting inherently nucleophilic alkyl radicals with electrophilic sulfone‐bearing surrogates, thus inverting the usual mode of reactivity. Along with alkylation, either an heteroaryl or oximino group is concurrently incorporated into the alkenes by a consecutive docking and migration process, leading to valuable products. The reaction displays a broad functional‐group tolerance under mild reaction conditions. The protocol opens new vistas for the late‐stage modification of complex natural products and drug molecules containing alkene moieties.     

Keteniminium‐Driven Umpolung Difunctionalization of Ynamides

A three‐component Pd‐catalyzed coupling of ynamides, aryl diazonium salts, and aryl boronic acids for the synthesis of novel triaryl‐substituted enamides is described. This transformation represents the first example of an umpolung regioselective unsymmetrical syn‐1,2‐diarylation/aryl‐olefination of ynamides. The aryl moieties of the diazonium salt (electrophile) and boronic acid (nucleophile) are explicitly incorporated in the electrophilic α‐ and nucleophilic β‐position, respectively, of the ynamide, resulting in a single isomer of the N‐bearing tetrasubstituted olefin. The scope is broad (68 examples), showing excellent functional‐group tolerance. DFT calculations substantiate the rationale of the mechanistic cycle and the regioselectivity. The chemoselectivity and synthetic potential of the enamide products were also studied.